ABSTRACT: BACKGROUND:Tuberculosis (TB) and human immunodeficiency virus (HIV) are the leading causes of infectious-disease-related deaths in Ethiopia, but little is known about their spatial distribution across the country. The aim of this study was to investigate the spatial patterns of TB and HIV co-infection in Ethiopia at the district level. METHODS:We conducted an ecological study using TB and HIV data reported from all regions of Ethiopia through the national Health Management Information System (HMIS), between June 2015 and June 2017. Spatial clustering was assessed using Moran's I statistic and Getis-Ord statistic. Spatial binomial regression models were constructed separately for the prevalence of TB among people living with HIV and for the prevalence of HIV among TB patients, with and without spatial components using a Bayesian approach. RESULTS:A total of 1,830,880 HIV and 192,359 TB patients were included in the analysis. The prevalence of HIV among TB patients was 7.34%; hotspots were observed in districts located in Amhara, Afar, and Gambela regions, and cold spots were observed in Oromiya and Southern Nations, Nationalities, and People (SNNP) regions. The prevalence of TB among people living with HIV varied from 0.7% in Oromia region to 14.5% in Afar region. Hotspots of TB prevalence among people living with HIV were observed in districts located in Gambela, Afar, Somali, and Oromiya regions; whereas the cold spots were observed in districts located in Amhara and Tigray regions. The ecological-level factors associated with the prevalence of TB among people living with HIV were low wealth index (OR: 1.49; 95% CrI: 1.05, 2.05), low adult literacy rate (OR: 0.67; 95% CrI: 0.46, 0.94), and distance to an international border (OR: 0.61; 95% CrI: 0.40, 0.91). The factors associated with the prevalence of HIV among TB patients were poor health care access (OR: 0.76; 95% CrI: 0.59, 0.95), low wealth index (OR: 1.31; 95% CrI: 1.01, 1.67), and low adult literacy rate (OR: 1.37; 95% CrI: 1.03, 1.78). CONCLUSION:Our study provides evidence for geographic clustering of TB/HIV co-infection in Ethiopia. Health care access, proximity to international borders, and demographic factors such as low wealth index and adult literacy were significantly associated with the prevalence of TB/HIV co-infection.